A gene for non-syndromic autosomal dominant progressive postlingual sensorineural hearing loss maps to chromosome 14q12-13

We report a novel locus responsible for postlingual progressive sensorineural hearing loss (designated DFNA9) that maps to chromosome 14q12-13. A large kindred with autosomal dominant transmission of non- syndromic hearing loss was clinically studied. Hearing in affected individuals deteriorated at approximately 20 years of age and progressed to anacusis in the fifth decade. A random genome-wide search using polymorphic short tandem repeats demonstrated linkage with D14S121 (maximum two point LOD score = 6.19, theta = 0). Haplotype analysis of recombination events defined a 9 cM disease interval, between D14S252 and D14S49.      

1142280946Effect of estradiol and PAMPs on class II mediated antigen presentation and immunomodulatory molecule expression in the mouse female reproductive tract

Problem:  Antigen presenting cells (APC) in the female reproductive tract play important roles in innate immune defense and activation of the adaptive immune responses. The objective of this study was to examine the effects of estradiol and PAMP on antigen presentation in the female reproductive tract.
Method of Study:  DO11.10 T cell antigen receptor transgenic mice specific for the MHC class II-restricted OVA323–339peptide were used to study the effects of estradiol and PAMP on antigen presentation of OVA by uterine epithelial (EC) and stromal cells as well as vaginal cells to OVA specific memory-T cells.
Results:  Estradiol inhibited antigen presentation of OVA by uterine EC, uterine stromal cells and vaginal cells to OVA specific memory-T cells. When ovariectomized animals were treated with estradiol for 1 or 3 days, antigen presentation decreased by 20–80%. In contrast, incubation with TLR agonists increased antigen presentation by EC (Poly (I:C), Pam3Cys), stromal cells (PGN, Pam3Cys) and vaginal cells (LPS, Pam3Cys). Analysis of mRNA expression by real time RT-PCR indicated that estradiol inhibited CD40, CD80/86 and class II in the uterus and vagina. In contrast, stimulation of antigen presentation by PAMP did not correlate with changes in costimulatory molecule mRNA expression.
Conclusions:  These results indicate that APC in the uterus and vagina are responsive to estradiol, which inhibits antigen presentation and costimulatory molecule expression. These findings suggest that whereas APC in the uterus and vagina respond to TLR agonists with increased antigen presentation, which initiates an adaptive immune response, their effects appear to be at levels other than the expression of costimulatory molecules.
Acknowledgement:  Supported by AI-13541 from NIH.     

Relationship of clomiphene dose and patient weight to successful treatment

Our objective was to examine the relationship between patient weight and the dose of clomiphene required for pregnancy so as to assess the validity of recommendations that the dose of clomiphene be limited to 100 mg. We retrospectively analysed the weight-dose relationship in 1681 clomiphene pregnancies and the relationship between dose and pregnancy, births, multiple births, number of pre-ovulatory follicles and endometrial thickness in 2841 cycles of clomiphene treatment, 25- 250 mg, for 5 days before intrauterine insemination (IUI). Doses of clomiphene >100 mg/day were used before pregnancies in 27.4% of patients who weighed >90 kg and in 14.7% of all pregnancies. In IUI cycles, pregnancies and births, but not multiple births or abortions, were related to dose. An increase in dose from 25 to 100 mg resulted in higher pregnancy and birth rates, and in an increase in the average number of pre-ovulatory follicles > or =12 mm in diameter, from 2.0 to 2.8, with no additional increase at higher doses. Endometrial thickness and cycle day of insemination were not related to dose. We conclude that doses of clomiphene may safely be increased beyond 100 mg, and that doses > or =100 mg are required in significant numbers of patients.      

因卡膦酸二钠的合成

目的：合成因卡膦酸二钠,并进行工艺改进。方法：即以环庚胺、亚磷酸二乙酯、原甲酸三乙酸为为起始原料,经二步反应合成因卡膦酸二钠。结果：避免了硅胶柱分离工艺,产物经IR、NMR、MS及元素分析、热分析确证了化学结构。结论：合成方便收率稳定,工艺简单。